This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Long term depression of synaptic strength in Purkinje neurons requires repeated inositol-1,4,5-trisphosphate (InsP3)-mediated Ca2+ release, but the InsP3 receptor, while highly abundant, is extraordinarily insensitive to InsP3 in this cell. Synaptic inputs occur at distinct structures, called spines, that are ca. 15m diameter spheres connected to the dendrite via a narrow neck. The ability of the spine to compartmentalize electrical and chemical signals is poorly understood. We are using this project to drive the development of new electrophysiological modeling capabilities of Virtual Cell.